Improved classificaiton of acute and chronic leukemias and lymphomas, quantitation of cell kill induced by chemotherapy, and monitoring of patients at all stages of their disease are the main aims of this project. More than 3,900 samples from over 1,200 patients were studied, using flow cytometry techniques for the measurement of DNA, RNA, nuclear diameter and chromatin structure in situ. The relative RNA content of G 0/1 cells-expressed as RNA index (R.I.)-is an excellent measure for the objective classification into acute lymphoblastic (ALL) and non-lymphoblastic (ANLL) leukemia: RI is 10.7 plus or minus 2.0 in ALL, and 20.7 plus or minus 3.8 in ANLL. The same differences were found in lymphoblastic and myeloblastic transformation of chronic myelogenous leukemia. Measurement of DNA content allowed to determine stemlines and cell cycle distribution. Aneuploid stemlines were found in 40 percent of childhood ALL and in 30 percent of adult ANLL. A group of markedly hypodiploid patients will ALL responded only poorly to standard intensive ALL therapy. In adult ANLL, fewer patients with aneuploid stemlines achieved complete remission (CR) compared to those with diploid stemlines. In a number of patients, more than one stemline could be identified ("biclonal"). In others, the phenotypic characteristics of lymphoblasts and myeloblasts were found (biphenotypic) and attempts will be made to separate these cell populations. Results in human leukemias were greatly improved by using bone marrow biopsies. They also helped in monitoring patients with aneuploid DNA stemlines during remission. As few as 1 percent aneuploid cells could be identified. Attempts to classify the Non-Hodgkin lymphomas (NHL) will be undertaken. Preliminary results show that low proliferation and low RNA content was characteristic for "low grade" malignant NHL, while high proliferation, high RNA content and the frequent occurrence of aneuploid stemlines was indicative of "high grade" NHL. A new method was developed by us to quantitate the number of leukemic and normal cells per mm3 bone marrow. Sequential studies of patients on chemotherapy allowed determination of cell kill kinetics. The method covers a range of 4-5 log 10. A less than or equal to 2 log 10 cell kill in the first 5 days of ANLL induction therapy predicted (Text Truncated - Exceeds Capacity)